Disease-related alterations in serum drug binding can influence drug distribution, elimination, and the intensity of drug effect. Binding alterations may relate to qualitative and quantitative changes in the serum protein(s) responsible for drug binding, and to altered levels of endogenous competing substances. The levels of several serum proteins are markedly altered by burn injury. For example, our studies in burn patients show that postburn serum albumin levels decrease to 2.2 g/dl (control, 4.4 g/dl, p is less than 0.001). While Alpha 1-acid glycoprotein levels increase to 222 mg/dl (control, 83 mg/dl, p=0.001). Our preliminary data also indicate that the serum free fraction of drug may increase (for diozepam, form 0.017 to 0.055, P=0.015; for phenytoin, from 0.16 to 0.24, P is less than 0.001) or decrease (for propranolol, from 0.107 to 0.045, p is less than 0.001), probably due in part to alterations in binding protein concentration. Also, varying levels of endogenous competing substances may influence postburn serum drug binding. The relationship between postburn alterations in the levels of serum components (binding proteins and endogenous competing substances) and these significant postburn alterations in serum drug binding has not been studied. We propose to systematically characterize postburn serum drug binding by: 1) quantifying the extent of postburn binding alterations, 2) relating binding alterations to alterations in the levels of serum components, and 3) examining the postburn time-dependency of drug binding alterations. To accomplish these objectives, we will examine the binding of 8 drugs (diazepam, imipramine, lidocaine, meperidine, phenytoin, propranolol, salicylate and warfarin) in the serum of 20 burn patients (at two postburn timepoints, acute and healed) and in 12 control subjects. We will use equilbrium dialysis to measure serum free fraction of drug and we will estimate binding affinity and capacity for each drug in each subject. Concentrations of several serum components (total protein, albumin, Alpha l-, Alpha 2-, Beta-, and Gamma-globuulins, Alpha l-acid glycoprotein, fatty acids, billirubin and triglycerides) will be measured. Appropriate comparisons and correlations will be made using the data collected. The information gained will provide needed mechanistic insight into postburn drug disposition and could thereby influence drug dosing for burn patients.